What are the risks of Graft-Versus-Host Disease (GVHD) after a Stem Cell Transplant?

From the Guidelines

Graft-Versus-Host Disease (GVHD) is a significant risk after a Stem Cell Transplant, with the incidence of acute GVHD (grade 2-4) ranging from 12.6% to 16% and chronic GVHD ranging from 14.6% to 23%, depending on the age of the patient and the type of transplant 1. The risks of GVHD after a stem cell transplant are multifaceted and can be influenced by various factors, including:

• Age of the patient: Older patients are at a higher risk of developing GVHD 1
• Type of transplant: The risk of GVHD varies depending on the type of transplant, with allogeneic transplants carrying a higher risk than autologous transplants 1
• Conditioning regimen: The intensity of the conditioning regimen can impact the risk of GVHD, with myeloablative conditioning regimens carrying a higher risk than reduced-intensity conditioning regimens 1
• Donor-recipient HLA mismatch: A mismatch between the donor and recipient's HLA can increase the risk of GVHD 1 Some of the key complications associated with GVHD include:
• Death: GVHD can be fatal, especially if left untreated or if treatment is delayed 1
• Organ damage: GVHD can cause damage to various organs, including the skin, liver, and gut 1
• Infection: Patients with GVHD are at a higher risk of developing infections, which can be life-threatening 1
• Infertility: GVHD can also impact fertility, especially in patients who receive myeloablative conditioning regimens 1 To manage GVHD, a multi-tiered approach is often used, including:
• Corticosteroids as first-line therapy 1
• Calcineurin inhibitors, such as tacrolimus or cyclosporine, as second-line therapy 1
• Mycophenolate mofetil or sirolimus as additional second-line options 1
• Extracorporeal photopheresis or ruxolitinib as salvage therapies 1 Prophylaxis is also crucial in preventing GVHD, and typically combines a calcineurin inhibitor with methotrexate or mycophenolate mofetil 1. Supportive care, including antimicrobial prophylaxis, nutritional support, and symptom management, is essential in managing GVHD 1. Regular monitoring of organ function and medication levels is crucial for optimal management of GVHD 1.

From the Research

Risks of Graft-Versus-Host Disease (GVHD) after a Stem Cell Transplant

The risks of GVHD after a stem cell transplant are significant, with chronic GVHD occurring in approximately 60% of patients who survive for more than 100 days after receiving an allogeneic marrow or peripheral blood stem cell transplant without T-cell depletion of the graft 2. The risk factors for development of chronic GVHD include:

• Degree of human leukocyte antigen (HLA) disparity
• Increasing recipient age
• Use of peripheral blood stem cells as a source
• Myeloablative conditioning regimens
• Prior acute GVHD (aGVHD)
• Female donor to male recipient 3

Clinical Manifestations and Diagnosis

Chronic GVHD represents a major cause of morbidity and mortality among hematopoietic stem cell transplant recipients, with clinical manifestations leading to a diagnosis of chronic GVHD 2. The diagnosis of chronic GVHD is based on clinical manifestations, and the approach for therapy includes glucocorticoids and extended administration of a calcineurin inhibitor 2.

Treatment and Management

The treatment of GVHD is challenging, with corticosteroids being the standard first-line therapy, but only effective in roughly half of all cases 4. New and emerging therapies for acute and chronic GVHD are being developed, including targeted therapies such as Bruton's tyrosine kinase inhibition, JAK1/2 inhibition, and ROCK2 inhibitors 3. The use of monoclonal antibodies for the treatment of GVHD following allogeneic stem cell transplantation has also been investigated, with response rates reported to be greater than 60% 5.

Prophylaxis and Prevention

Approaches to prevent GVHD include pharmacologic strategies such as calcineurin inhibitors (cyclosporine, tacrolimus) combined with methotrexate or mTOR inhibitors (sirolimus), and IMP dehydrogenase inhibitors (mycophenolate mofetil) 3. Increasingly, posttransplant cyclophosphamide is emerging as a promising strategy for GVCHD prevention, especially in a setting of reduced intensity conditioning 3. A comparative efficacy study of 20 GVHD prophylaxis therapies found that cyclosporine + methotrexate + Anti-T cell globulin (ATG) may be the best choice when starting treatment for GVHD 6.